Kenshi Fujii

Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction.

BackgroundWe investigated myocardial perfusion dynamics after thrombolysis and its clinical implications. Methods and ResultsWe studied 39 patients with acute anterior myocardial infarction (AMI). Myocardial contrast echocardiography (MCE) was performed before and immediately after successful reflow with intracoronary injection of sonicated loxaglate. The average segmental score by twodimensional echocardiography (graded 0, normal, to 3, akinetic/dyskinetic) and global ejection fraction (left ventricular ejection fraction, LVEF%) by left ventriculography were measured at 1 day and at 4 weeks after reflow. Hypokinesis in the infarct region was assessed by the centerline method and expressed in terms of standard deviations (regional wall motion [RWM:SD/chord) of normal. Immediately after reflow, 30 of 39 patients (group A) showed significant contrast enhancement within the risk area. The other nine patients (23%, group B), however, showed the residual contrast defect in the risk area (myocardial no reflow). There were no significant differences in the elapsed time, angiographic collateral grade, and degree of residual stenosis between group A and group B. Before reflow, both groups exhibited similar levels of global and regional left ventricular function. Improvement in global (LVEF, average segmental score) and regional left ventricular function was greater in group A than in group B (average segmental score, 0.44±0.41 versus 0.97±0.36, p < 0.01; LVEF, 56.4± 13.4 versus 42.7±8.9, p < 0.0S; RWM, −1.87±0.85 versus −3.18±0.52, p < O.O05). ConclusionsMCE demonstrates that angiographically successful reflow cannot be used as an indicator of successful myocardial reperfusion in AMI patients. The residual contrast defect in the risk area demonstrated immediately after reflow is a predictor of poor functional recovery of the postischemic myocardium.

Myocardial Perfusion Patterns Related to Thrombolysis in Myocardial Infarction Perfusion Grades After Coronary Angioplasty in Patients With Acute Anterior Wall Myocardial Infarction

BACKGROUND Epicardial coronary flow is occasionally reduced even after coronary intervention despite the absence of vessel obstruction in patients with acute myocardial infarction. Our aim was to clarify the cause and outcomes of radiocontrast slow filling in patients with reperfused acute anterior myocardial infarction by assessing microvascular damage with the use of myocardial contrast echocardiography (MCE) and functional outcomes. METHODS AND RESULTS We carefully reviewed the cineangiograms of 86 patients who achieved coronary revascularization within 12 hours of the onset and underwent MCE before and soon after recanalization with the intracoronary injection of sonicated microbubbles. Antegrade coronary flow after recanalization was graded by two observers based on Thrombolysis in Myocardial Infarction (TIMI) trial flow grades. Left ventricular ejection fraction was measured on the day of infarction and 1 month later. TIMI grade 2 was observed in 18 patients (21%), and the other 68 patients manifested TIMI grade 3 after recanalization. All patients with TIMI 2 showed substantial MCE no reflow, whereas only 11 patients (16%) with TIMI 3 showed MCE no reflow. Functional improvement was worse in patients with TIMI 2 than in those with TIMI 3 (TIMI 2, 38 +/- 8% versus 40 +/- 8%, P = NS [acute versus late]; TIMI 3, 44 +/- 13% versus 55 +/- 13%, P < .001). Among patients with TIMI 3, significant functional improvement was observed only in patients with MCE reflow (MCE reflow, 46 +/- 13% versus 57 +/- 12%, P < .001; MCE no reflow, 35 +/- 11% versus 45 +/- 12%, P = NS). CONCLUSIONS Despite no obstructive lesion of the vessel, TIMI 2 is caused by advanced microvascular damage and is a highly specific, although not sensitive, predictor of poor functional outcomes in patients with acute myocardial infarction. TIMI 3 does not necessarily indicate myocardial salvage, and detection of MCE no reflow in these patients is particularly useful for the prediction of functional outcome.

Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials.

BACKGROUND Patients who have acute myocardial infarction remain at major risk of cardiovascular events. We aimed to assess the effects of either human atrial natriuretic peptide or nicorandil on infarct size and cardiovascular outcome. METHODS We enrolled 1216 patients who had acute myocardial infarction and were undergoing reperfusion treatment in two prospective, single-blind trials at 65 hospitals in Japan. We randomly assigned 277 patients to receive intravenous atrial natriuretic peptide (0.025 microg/kg per min for 3 days) and 292 the same dose of placebo. 276 patients were assigned to receive intravenous nicorandil (0.067 mg/kg as a bolus, followed by 1.67 microg/kg per min as a 24-h continuous infusion), and 269 the same dose of placebo. Median follow-up was 2.7 (IQR 1.5-3.6) years for patients in the atrial natriuretic peptide trial and 2.5 (1.5-3.7) years for those in the nicorandil trial. Primary endpoints were infarct size (estimated from creatine kinase) and left ventricular ejection fraction (gauged by angiography of the left ventricle). FINDINGS 43 patients withdrew consent after randomisation, and 59 did not have acute myocardial infarction. We did not assess infarct size in 50 patients for whom we had fewer than six samples of blood. We did not have angiographs of left ventricles in 383 patients. Total creatine kinase was 66,459.9 IU/mL per h in patients given atrial natriuretic peptide, compared with 77,878.9 IU/mL per h in controls, with a ratio of 0.85 between these groups (95% CI 0.75-0.97, p=0.016), which indicated a reduction of 14.7% in infarct size (95% CI 3.0-24.9%). The left ventricular ejection fraction at 6-12 months increased in the atrial natriuretic peptide group (ratio 1.05, 95% CI 1.01-1.10, p=0.024). Total activity of creatine kinase did not differ between patients given nicorandil (70 520.5 IU/mL per h) and controls (70 852.7 IU/mL per h) (ratio 0.995, 95% CI 0.878-1.138, p=0.94). Intravenous nicorandil did not affect the size of the left ventricular ejection fraction, although oral administration of nicorandil during follow-up increased the left ventricular ejection fraction between the chronic and acute phases. 29 patients in the atrial natriuretic peptide group had severe hypotension, compared with one in the corresponding placebo group. INTERPRETATION Patients with acute myocardial infarction who were given atrial natriuretic peptide had lower infarct size, fewer reperfusion injuries, and better outcomes than controls. We believe that atrial natriuretic peptide could be a safe and effective adjunctive treatment in patients with acute myocardial infarction who receive percutaneous coronary intervention.

Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction

OBJECTIVES We assessed whether the intravenous administration of nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts beneficial effect on microvascular function and functional and clinical outcomes in patients with acute myocardial infarction (AMI). BACKGROUND Experimental studies documented that ATP-sensitive K+ channel opener exerts cardioprotection after prolonged ischemia. METHODS We randomly divided 81 patients with a first anterior AMI into two groups, nicorandil (n = 40) and control groups (n = 41). All patients received successful coronary angioplasty within 12 h after the symptom onset and underwent myocardial contrast echcardiography (MCE) with the intracoronary injection of sonicated microbubbles. In the nicorandil group, we injected 4 mg of nicorandil followed by the infusion at 6 mg/h for 24 h and by oral nicorandil (15 mg/day). RESULTS The improvement in regional left ventricular function, wall motion score and regional wall motion was significantly better in the nicorandil group then in the control group. Intractable congestive heart failure, malignant ventricular arrhythmia and pericardial effusion were more frequently found in the control group than in the nicorandil group (15% vs. 37%, 5% vs. 20% and 8% vs. 37%, p < 0.05, respectively). The frequency of sizable MCE no reflow phenomenon was significantly lower in the nicorandil group than in the control group (15% vs. 33%, p < 0.05). CONCLUSIONS Intravenous nicorandil in conjunction with coronary angioplasty is associated with better functional and clinical outcomes compared to angioplasty alone in patients with an anterior AMI. Myocardial contrast echocardiography findings imply that an improvement in microvascular function with nicorandil may be attributable to this better outcome.

Association between hyperglycemia and the no-reflow phenomenon inpatients with acute myocardial infarction

OBJECTIVES We investigated the association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction (AMI). BACKGROUND Hyperglycemia is associated with increased risks of heart failure, cardiogenic shock, and death after AMI, but its underlying mechanism remains unknown. METHODS A total of 146 consecutive patients with a first AMI were studied by intracoronary myocardial contrast echocardiography (MCE) after successful reperfusion within 24 h after symptom onset. Two-dimensional echocardiography was recorded on day 1 and three months later to determine the change in the wall motion score (DeltaWMS; sum of 16 segmental scores; dyskinesia = 4 to normokinesia = 0). RESULTS The no-reflow phenomenon was found on MCE in 49 (33.6%) of 146 patients; their glucose level on hospital admission was significantly higher than that of patients who did not exhibit this phenomenon (209 +/- 79 vs. 159 +/- 56 mg/dl; p < 0.0001). There was no difference in glycosylated hemoglobin or in the incidence of diabetes mellitus between the two subsets. The no-reflow phenomenon was more often observed in the 75 patients with hyperglycemia (>/=160 mg/dl) than in those without hyperglycemia (52.0% vs. 14.1%; p < 0.0001). Patients with hyperglycemia had a higher peak creatine kinase level (2,497 +/- 1,603 vs. 1,804 +/- 1,300 IU/l; p = 0.005) and a lower DeltaWMS (3.7 +/- 4.8 vs. 5.7 +/- 4.3; p = 0.01) than did those without hyperglycemia. The blood glucose level was an independent prognostic factor for no reflow, along with age, gender, absence of pre-infarction angina, complete occlusion of the culprit lesion, and anterior AMI. CONCLUSIONS Hyperglycemia might be associated with impaired microvascular function after AMI, resulting in a larger infarct size and worse functional recovery.

Value and limitations of Doppler echocardiography in the quantification of stenotic mitral valve area: comparison of the pressure half-time and the continuity equation methods.

Two Doppler methods, the pressure half-time method proposed by Hatle and the method based on the equation of continuity, were used to estimate stenotic mitral valve area noninvasively, and the accuracy of these methods was examined in patients with and without associated aortic regurgitation. Mitral valve area determined at catheterization by the Gorlin formula was used as a standard of reference. The study population consisted of 41 patients with mitral stenosis, and 20 of the 41 patients had associated aortic regurgitation. According to the equation of continuity, mitral valve area was determined as a product of aortic or pulmonic annular cross-sectional area and the ratio of time velocity integral of aortic or pulmonic flow to that of the mitral stenotic jet. Mitral valve area was determined by the pressure half-time method as 220/pressure half-time, the time from the peak transmitral velocity to one-half the square root of the peak velocity on the continuous-wave Doppler-determined transmitral flow velocity pattern. The pressure half-time method tended to overestimate catheterization measurements, and the correlation coefficient for this relation was .69 (SEE = 0.44 cm2). The correlation coefficient improved to .90 when the patients with associated aortic regurgitation were excluded. Mitral valve areas determined by the continuity equation method correlated well with catheterization measurements at a correlation coefficient of .91 (SEE = 0.24 cm2), irrespective of the presence of aortic regurgitation. The ratio of the time-velocity integral or aortic or pulmonic flow to the time-velocity integral of mitral stenotic jet also correlated well with mitral valve area determined by catheterization at a correlation coefficient of .84 (SEE = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Predictive Factors for Development of the No-Reflow Phenomenon in Patients With Reperfused Anterior Wall Acute Myocardial Infarction

OBJECTIVES We sought to elucidate the clinical factors related to the development of no-reflow phenomenon after successful coronary reperfusion in patients with an acute myocardial infarction (AMI). BACKGROUND Myocardial contrast echocardiography revealed that the no-reflow phenomenon is observed in some patients with a reperfused AMI, and those patients usually have poor functional and clinical outcomes. It is still unknown what clinical factors are related to the development of the no-reflow phenomenon. METHODS Myocardial contrast echocardiography was performed 15 min after successful coronary reperfusion therapy in 199 patients with an anterior wall AMI who underwent successful coronary reperfusion with primary coronary angioplasty within 24 h after the onset of AMI. Multiple logistic regression analysis was used to identify independent predictors of the no-reflow phenomenon. RESULTS Seventy-nine patients showed the no-reflow phenomenon. Univariate analysis indicated that pre-infarction angina within 48 h before symptom onset, Killip class, Thrombolysis in Myocardial Infarction flow grade 0 on the initial coronary angiogram, the number of abnormal Q-waves and the wall motion score (WMS) on the echocardiogram obtained at hospital admission are related to the no-reflow phenomenon. Multivariate logistic regression analysis revealed that all of these factors, except for Killip class, are independent predictive factors of the no-reflow phenomenon. CONCLUSIONS Development of the no-reflow phenomenon is related to the severity of myocardial damage (number of Q-waves), the size of the risk area (WMS) and the occlusion status of infarct-related artery. In addition, ischemic preconditioning (pre-infarction angina) seems to be the factor that attenuates the no-reflow phenomenon.

Dobutamine Stress Echocardiography Predicts Reversible Dysfunction and Quantitates the Extent of Irreversibly Damaged Myocardium After Reperfusion of Anterior Myocardial Infarction

OBJECTIVES This study was designed to evaluate dobutamine stress echocardiography in identifying reversible dysfunction and assessing the extent of irreversibly damaged myocardium early in acute myocardial infarction. BACKGROUND Several experimental and clinical studies have suggested that dobutamine enhances contractile function of stunned or hibernating, or both, myocardium. It is important for clinical strategy to predict the magnitude of improvement in myocardial function early in acute myocardial infarction. METHODS We studied 21 patients with a reperfused first anterior myocardial infarction. Two-dimensional echocardiography was performed before and during dobutamine infusion (10 micrograms/kg body weight per min) at a mean of 3 days after the infarction. Follow-up echocardiography was performed at a mean of 25 days later. To assess segmental wall motion, we divided the left ventricle into 17 segments and assigned a wall motion abnormality score: 3 = dyskinesia or akinesia; 0 = normal. Improvement in wall motion was indicated by a decrease of at least one grade in segmental score. For quantitative assessment, the ratio of endocardial length showing dyskinesia or akinesia to a left ventricular endocardial length (akinetic length ratio) was determined in the apical long-axis view at each stage. RESULTS Sensitivity and specificity of dobutamine infusion in detecting improvement in wall motion at follow-up echocardiography were 83% (55 of 66 segments) and 86% (43 of 50 segments), respectively. Excellent correlation was found (r = 0.93, p < 0.001; absolute difference [mean +/- SD] 0.03 +/- 0.05) between the akinetic length ratios measured during dobutamine infusion and in the late convalescent stage. CONCLUSIONS In the early stage of acute myocardial infarction, low dose dobutamine stress echocardiography provides a useful method for predicting reversible dysfunction with excellent sensitivity and specificity and can also be used to quantitate the extent of irreversibly damaged myocardium.

Effect of angina pectoris on myocardial protection in patients with reperfused anterior wall myocardial infarction: retrospective clinical evidence of "preconditioning".

OBJECTIVES We examined whether angina pectoris occurring shortly before the onset of acute myocardial infarction can actually preserve postischemic left ventricular function in humans. BACKGROUND Experimental studies indicate that brief, transient episodes of ischemia render the heart very resistant to infarction from a subsequent sustained ischemic insult, an effect termed ischemic preconditioning. However, no clinical data are available concerning the implications of angina pectoris shortly before the onset of infarction in humans. METHODS We studied 84 patients with an acute anterior myocardial infarction. All patients had total occlusion of the proximal or medial portion of the left anterior descending coronary artery and achieved reflow within 6 h of onset. Patients were classified into three groups on the basis of duration of antecedent angina pectoris: group 1 = no angina (37 patients); group 2 = new angina pectoris occurring < or = 7 days of onset of infarction (22 patients); group 3 = angina pectoris beginning > 7 days before onset of infarction (25 patients). All patients underwent left ventriculography on the day of, and 28 days after, onset of infarction to determine ejection fraction and regional wall motion in the territory of the left anterior descending coronary artery by the centerline method. RESULTS Angiographic collateral flow grade was higher in group 3 than in groups 1 and 2 ([mean +/- SD] group 1 = 0.08 +/- 0.7, group 2 = 0.7 +/- 0.7, group 3 = 1.5 +/- 0.8). Although there were no differences in baseline ejection fraction and regional wall motion among the three groups, the degree of improvement was significantly greater in groups 2 and 3 than in group 1 (late minus baseline ejection fraction: group 1 = 0 +/- 8%, group 2 = 7 +/- 10% group 3 = 6 +/- 10% [p < 0.05 group 1 vs. groups 2 and 3]; late minus baseline regional wall motion: group 1 = 0.2 +/- 0.4, group 2 = 0.6 +/- 0.5, group 3 = 0.5 +/- 0.6 SD/chord [p < 0.05, group 1 vs. group 2]). When the study was limited to those patients with no or poor collateral flow (31 in group 1, 19 in group 2, 10 in group 3), only group 2 patients had a significant improvement in wall motion. Angina pectoris within 24 h before onset of infarction was more frequent in group 2 (82%) than group 3 (28%, p < 0.05). CONCLUSIONS Episodes of angina pectoris occurring shortly before the onset of infarction may preserve myocardial contractile function in reperfused myocardial infarction despite less support from collateral flow channels, although these are suggestive results in a limited number of patients.

Time course of functional improvement in stunned myocardium in risk area in patients with reperfused anterior infarction.

BackgroundThe beneficial effect of coronary reflow on myocardial salvage may be assessed more accurately than in previous studies if the size of risk area is taken into account, particularly because the size of risk area varies significantly among patients. In this study, the risk area was determined with myocardial contrast echocardiography to investigate the time course of functional recovery of postischemic myocardium within the risk area in patients with reperfused anterior myocardial infarction. Methods and ResultsThe study population consisted of 21 patients with anterior myocardial infarction who achieved coronary reflow within 6 hours of onset by means of thrombolysis or coronary angioplasty. Myocardial contrast echocardiography was performed with the injection of hand-agitated Haemaccel (5 ml) into the right and left coronary arteries before coronary reflow, and the risk area was defined as the area of contrast perfusion defect in the apical long-axis view. The ratio of the endocardial length of abnormal contraction (dyskinesis/akinesis) segment to that of contrast defect segment (AS/CD) was determined at days 1, 2, 3, 7, 14, and 28 of reflow. Before reflow, the length of contrast defect correlated well with the segment length of dyskinesis/akinesis. The values for AS/CD in patients with successful reperfusion significantly and progressively decreased until day 14; 1.00±0.02 at day 1, 0.93±0.11 at day 2 (p<0.05 versus day 1), 0.84±0.16 at day 3 (p<0.05 versus day 2), 0.80±0.13 at day 7 (p<0.01 versus day 2), 0.73±0.10 at day 14, and 0.72±0.10 at day 28. Greater improvement in function was obtained in patients reperfused within 4 hours than in those reperfused at 24 hours (AS/CD at day 28, 0.64±0.12 versus 0.75±0.09, p<0.05). ConclusionThus, a significant amount of myocardium, an average of 28%o in segment length of the risk area, is salvaged in patients with reperfused anterior myocardial infarction. Major functional improvement seems to be achieved within 14 days of reflow.